The goals of the present study are to examine mechanisms by which autoantibodies to double-stranded DNA can localize to intracellular and specifically intranuclear targets in affected cells. The Principal Investigator has identified an anti-DNA antibody, mAb 3E10, that will selectively bind to kidney tubular epithelial cells and nuclei. The goals of the present study, are to characterize and detail the autoantibody determinants that are necessary for entry across the plasma membrane into the affected cells using site directed mutagenesis and chimeric antibodies and then to characterize the antibody determinants that are utilized for transport into the nucleus of the cell, and compare the two. The other Specific Aim is to directly label this antibody in order to develop systems that are useful for the identification of potential inhibitors of intracellular and intranuclear localization.